Interstitial cystitis (IC) is a chronic bladder disease with often devastating effects on the lives of approximately 450,000 people in the U.S. The etiology of IC is unknown, and there is currently no reliably effective treatment. It is therefore important to continue to search for a cause of this debilitating disorder in order to systematically devise an effective therapy. The applicants report discovering two, specific and significant abnormalities in the urine of IC patients as compared to controls, which may be linked to the pathogenesis of this disease - the presence of a low molecular weight urine peptide that inhibits the proliferation of bladder epithelial cells in vitro (antiproliferative factor, or APF) and complex changes in the levels of specific urine epithelial cell growth factors, including significantly decreased urine levels of heparin-binding epidermal growth factor-like growth factor. Because a damaged bladder epithelium is a central finding in IC, it is possible that the APF and the growth factor abnormalities are directly involved in the pathogenesis of this disease. The proposed research is designed to determine the mechanisms by which the APF regulates bladder epithelial cell proliferation. In addition, specific effects of HPLC-purified APF on bladder epithelial cell physiology in vitro will be confirmed in vivo using a mouse model. The applicants suggest data from these studies should yield valuable information regarding the regulation of bladder epithelial proliferation and the pathogenesis of IC.